In a pilot study, plasma levels of Gamma-amino butyric acid (GABA), a major inhibitory neurotransmitter in mammalian brain, and, an amino acid synthesized almost exclusively in the central nervous system, were found to be abnormal in patients with primary affective disorder. Specifically, plasma levels of GABA were lower than control in patients with primary unipolar affective disorder, and higher than control in patients with bipolar affective disorder while manic. Plasma GABA levels were comparable to control in bipolar depressed patients and in patients with secondary depression. The project outlined herein proposes to expand and extend the original study by: a) Enlarging the sample size for primary effective disorders; b) Obtaining plasma GABA levels from patients while symptomatic and after becoming normothymic, to investigate whether plasma GABA alterations in primary affective illness reflect a trait or state characteristic; c) Enlarging the group of secondary depressives to include depression secondary to medical or surgical illness. Diagnoses will be made by psychiatrists who are blind to the plasma GABA levels, and similarly, assay will be performed blind to the clinical diagnosis. Plasma GABA assays will be performed by gas chromatography/mass spectrometry or gas chromatography using procedures standardized in this laboratory. This project will determine whether plasma GABA provides a blood test for some kinds of affective disorder, and will provide experience with the practical clinical utility of the assay.